Glycogen is a polysaccharide that is the major carbohydrate in animal cells and a variety of bacteria including Escherichia coli, just like starch is in plants. Starch in plants and glycogen in bacteria are produced from a common substrate, ADPglucose (ADPG). In animals, on the other hand, glycogen is synthesized from UDP-glucose (UDPG) (1). The net rate of the synthesis of those storage polysaccharides in organisms is thought to be controlled by a variety of regulatory factors that respond to external environment as well as to internal physiological conditions. Such regulatory factors are expected to act, for example, in allosteric control of the reaction of ADPG (or UDPG) pyrophosphorylase (AGPase or UGPase, respectively) in the glycogenesis pathway, or by controlling the expression of genes coding for gluconeogenic enzymes (1-4).
Recent investigations have demonstrated that glycogen can be simultaneously synthesized and degraded during bacterial growth, thus making up a futile cycle wherein AGPase has a dual role in catalyzing the de novo synthesis of ADPG and in recycling the glucose units derived from the glycogen breakdown (5-7).
Simultaneous synthesis and degradation of glycogen and starch have been reported to occur also in animals and plants, respectively (8-10), thus indicating that the operation of futile cycling may entail advantages such as sensitive regulation and channelling of excess gluconeogenic intermediates toward various metabolic pathways in response to physiological and biochemical needs.
Presence of a one-way enzyme that catalyzes hydrolysis of ADPG (or UDPG) had been predicted in connection with this futile cycle-like route, which would allow more sensitive regulation of ADPG (UDPG) levels and therefore of the net rate of synthesis/degradation of storage polysaccharides. The first of such enzymes was discovered by Pozueta-Romero, J. and co-workers, who isolated and purified ADP-glucose pyrophosphatase (AGPPase) from barley and bacteria (11-13). The AGPPase they isolated was a one-way enzyme catalyzing hydrolysis of ADPG to glucose-1-phosphate (G1P) and adenosine 5′-monophosphate (AMP). Enzymes catalyzing the hydrolytic breakdown of UDPG have been reported to occur in mammalian cells (14-16). Playing a role in the control of glycoprotein, glycolipid and glycosaminoglycan biosynthesis (17-22), these enzymes show broad substrate specificity and have been found to be associated with nuclear, mitochondrial, endoplasmic reticulum and plasma membrane fractions.
Glycogen biosynthesis takes place in the cytosol. The possible involvement of enzymatic breakdown of UDPG in the control of carbon flow towards glycogen in mammalian cells has prompted us to identify a cytosolic protein, designated as UDP-glucose pyrophosphatase (UGPPase), that hydrolyzes UDPG with substantially the highest specificity.